Neurology- Pathology Flashcards
What are the main causes of dementia (marked by a decrease in cognitive ability, memory, or functioning with intact consciousness)?
- Alzheimer disease
- Frontotemporal dementia
- Lewy body dementia
- Creutzfeldt- Jakob disease
- Other
What pts are most at risk for Alzheimer?
elderly and Down syndrome pts.
What mutations mediate risk for Alzheimer?
ApoE2: decrease risk
ApoE4: increases risk
APP, presenilin-1, presenilin-2: increased risk of early onset
What are the main findings of Alzheimer’s?
widespread cortical atrophy
narrowing of the gyri and widening of sulci
decreased ACh
Senile plaques (below) in gray matter
Neurofibrillary tangles
What are senile plaques?
extracellular B-amyloid cores that may cause amyloid angiopathy leading to intracranial hemorrhage (AB amyloid synthesized by cleaving amyloid precursor protein (APP))
What are Neurofibrillary tangles?
intracellular, hyperphosphorylated tau protein (insoluble cytoskeletal elements). No of tangles correlates to the severity of disease
What is frontotemporal dementia (aka Pick disease)?
frontotemporal atrophy (spares parietal lobe and posterior 2/3 of the superior temporal gyrus) causes marked by dementia, aphasia, parkinsonian aspects, and change in personality
What are these?
Pick bodies: silver staining spherical tau protein aggregates
What is Lewy body dementia?
initially dementia and visual hallucinations followed by parkinsonian features
What causes Lewy body dementia?
a-synuclein defect (Lewy bodies, primarily cortical)
What is Creutzfield-Jakob disease?
rapidly progressive (weeks to months) dementia with myoclonus (“starte myoclonus)
What is myoclonus?
Myoclonus is a brief, involuntary twitching of a muscle or a group of muscles. It describes a medical sign and, generally, is not a diagnosis of a disease.
These myoclonic twitches, jerks, or seizures are usually caused by sudden muscle contractions (positive myoclonus) or brief lapses of contraction (negative myoclonus). The most common circumstance under which they occur is while falling asleep (hypnic jerk).
Myoclonic jerks occur in healthy persons and are experienced occasionally by everyone. However, when they appear with more persistence and become more widespread they can be a sign of various neurological disorders. Hiccups are a kind of myoclonic jerk specifically affecting the diaphragm. When a spasm is caused by another person it is known as a provoked spasm. Shudderingattacks in babies fall in this category.
Other features of Creutzfeldt-Jakob disease?
spongiform cortex affected
prions present
What are some other causes of dementia?
multi-infarct (aka vascular, 2nd most common cause of dementia in the elderly)
syphillis, HIV
vitamin B1, B3, or B12 deficiency
Wilson disease
normal pressure hydrocephalus
What is MS?
Autoimmune inflammatory and demyelination of the CNS (brain and spinal cord)
When is MS common to present initially?
more common in white living further from the equator
women in their 20-30s
How does MS present?
can present with:
optic neuritis (sudden loss of vision resultin in Marcus Gunn pupils)
INO
hemiparesis
hemisensory symptoms
bladder/bowerl incontinence
all with a remitting and relapsing course
What are the lab findings of MS?
increased CSF protein (IgG)
Oligoclonal bands are diagnostic
The gold standard for MS diagnosis is an MRI. How does it appear?
preiventricular plaques (area of oligodendrocyte loss and reactive gliosis) with destruction of axons
How is MS tx?
slow progression with disease-modifying therapies (e.g. B-interferon, natalizumab).
Tx acute flares with IV steroids
Symptomatic tx for neurogenic bladder (catheterization, muscarinic antagonists), spasicity (baclofen), pain (opiods)
What is acute inflammatory demyelinating polyradiculopathy?
the most common subtype of Guillian-Barre syndrome, and is an autoimmune condition that destroys Schwann cells causing inflammation and demyelination of peripheral nerves and motor fibers
How does acute inflammatory demyelinating polyradiculopathy present?
symmetric ascending muscle weakness and/or paralysis beginning in lower extremities
may see autonomic dysregulation (e.g. cardiac irregularities, HTN or hypotension) or sensory abnormalities
What is the prognosis for acute inflammatory demyelinating polyradiculopathy?
almost all survive and the majority recover completely after weeks to months
What are the lab findings of acute inflammatory demyelinating polyradiculopathy?
increased CSF protein with normal cell count (may cause papilledema)
What are some associations with acute inflammatory demyelinating polyradiculopathy?
infections (viral, Campylobacter)- autoimmune attack of peripheral myelin due to molecular mimicry
Tx of acute inflammatory demyelinating polyradiculopathy?
respiratory support is critical until recovery
additional: plasmapheresis, IV immunoglobulin
What are some other demyelinating and dysmyelinating diseases?
- Acute disseminated (postinfectious) encephalomyelitis
- Charcot- Marie-Tooth disease
- Krabbe disease
- Metachromatic leukodystrophy
- Progressive multifocal leukoencephalopathy
- adrenoleukodystrophy
Describe Acute disseminated (postinfectious) encephalomyelitis
multifocal perivntricular inflammation and demyelination after infection (commonly measles or VZV) or certain vaccinations (e.g. rabies, smallpox)
Describe Charcot-Marie-Tooth
aka hereditary motor and sensory neuropathy (HMSN)
group of progressive hereditary nerve disorders related to the defective production of proteins involved in the structure and function of peripheral nerves or the myelin sheath
What is the MOI of Charcot-Marie-Tooth?
AD
What are the main associations of Charcot-Marie-Tooth?
scoliosis and foot deformities
What is Krabbe disease?
AR lysosomal storage disease due to deficiency of galactocerebrosidase, causing buildup of galacocerebroside and psychosine that destroys meylin sheath
What are the main findings of Krabbe disease?
peripheral neuropathy
developmental delay
optic atrophy
globoid cells
Describe metachromatic leukodystrophy
AR lysosomal storage disease, most commonly due to arylsulfatase A deficiency, causing a buildup of sulfatides that leads to impaired production and destruction of myelin sheath
How does metachromatic leukodystrophy present?
central and peripheral demyelination with atexia and dementia
What is progressive multifocal leukoencephalopathy?
demyelination of CNS due to destruction of oligodendrocytes associated with JC virus
Who commonly gets progressive multifocal leukoencephalopathy?
seen in 2-4% of AIDS pts. (reactivation)
-risk with those using natalizumab and rituximab
What is the prognosis for progressive multifocal leukoencephalopathy?
rapidly progressive and usually fatal
What is adrenoleukodystrophy?
X-linked disorder (typically affecting males) that disrupts metabolism of very-long-chain fatty acids causing excessive buildup in nervous system, adrenal gland, and testes
Can lead to adrenal crisis and/or coma/death
What are the types of seizures?
partial (focal) and generalized
Where are partial seizures most common?
(affect single area of the brain) and most commonly originate in the medial temporal lobe (often preceded by seizure aura)
What are the types of partial seizures?
simple partial (consciousness intact)
complex- consciousness impaired
A disorder of recurrent seizures is called?
Epilepsy (febrile seizures are not epilepsy)
What is Status epilepticus?
continous or recurring seizure(s) that may result in brain injury
What are the types of generalized seizures?
Absence (petit mal)- 3 Hz, no postictal confusion, blank stare
Myoclonic- quick, repetitive jerks
Tonic-clonic (grand mal)- alternating stifferning and movement
Tonic- stiffening
Atonic- “drop” seizures (falls to floor)
What are the most common causes of seizures in children?
genetic, infection (febrile), trauma, metabolic
What are the most common causes of seizures in adults?
tumor, trauma, stroke, infection
What are the most common causes of seizures in the elderly?
stroke, tumor, trauma, metabolic, infection
What causes headaches?
mostly irritation of structures such as the dura, cranial nerves, or sometimes extracranial structures
What are the main types of HA?
- Cluster
- Tension
- Migraine
Describe cluster HA
unilateral HA usually lasting 15 min- 3 hr and described as repetitive, brief headaches with excruciating periorbital pain with lacrimation and rhinorrhea. (may induce Horner syndrome)
common in males
How is a cluster HA tx?
100% O2, sumatriptan
Describe tension HAs
Bilateral, typically lasting longer than 30 min (4-6 hr usual) and described as a steady pain, with no photophobia or phonophobia (no aura)
How are tension HAs tx?
analgesics, NSAIDs, amitriptyline for chronic
Describe migraines
Unilateral and typically lasting from 4-72 hrs, and described as a pulsating pain with nausea, photphobia or phonophobia (may have aura).
Due to irritation of CN V, meninges, or blood vessels (release of substance P)
How are migraines tx?
abortive therapies (e.g. triptans) and prophaylaxis (e.g. propanolol, topiramate, CCBs, and amitriptyline)
What are some other common causes of migraine?
subarchnoid hemorrhage (‘wost HA of my life’)
meningitis
hydrocephalus
neoplasia
arteritis (GCA)
What is vertigo? What are the main types?
sensation of spinnnng white actually stationary
-peripheral and central
Describe peripheral vertigo
more common and typically due to inner ear etiology (e.g. semicircular canal debris, vestibular nerve infeciton, Meniere disease). May cause delayed horizontal nystagmus
Describe central vertigo
brain stem or cerebellar lesion (.e.g stroke affecting vestibular nuclei or posterior fossa tumor).
Findings: directional change of nystagmus, skew deviation, diplopia, dysmetria
Positional testing: immediate nystagmus in any direction; may change directions
What are some common Neurocutaneous disorders?
- Sturge Weber syndrome
- Tuberous sclerosis
- Neurofibromatosus type I (von Recklinghausen disease)
- von Hippel Lindau disease
What causes Sturge Weber syndrome?
congenital, non-inherited (somatic), developmental anomaly of neural crest derivatives (mesoderm/ectoderm) due to activating mutation of GNAQ gene
How does Sturge Weber syndrome present?
small (capillary-sized) blood vessels are affected causing post-wine stain of the face (nevus flammeus, a non-neoplastic “birthmark” of CN V1/V2 distribution)
ipsilateral leptimeningeal angioma (below)
episclerosl hemangioma (raises IOP and can lead to early-onset glaucoma)
What can a ipsilateral leptimeningeal angioma in Sturge Weber cause?
seizures/epilepsy and/or intellectual disability
Sturge Weber syndrome symptoms mnemonic
STURGE-Weber
Sporadic/post-wine Stain, Tram track calcifications (opposing gyri), Unilateral, Retardation, Glaucoma/GNAQ gene, Epilepsy
How does tuberous sclerosis present?
HAMARTOMAS
Hamartomas in the CNS and skin
Angiofibromas
Mitral regurg
Ash-leaf spots
cardiac Rhabdomyomas
Tuberous sclerosis
autosomal dOminant
Mental retardation
renal Angiomyolipoma
Seziures/Shagreen patches
Angiofibroma (as seen in TS)
Ash-leaf spots (as seen in TS)
Tuberou sclerosis increases the risk of what?
subepdenymal astrocytomas and ungual fibromas
How does Neruofibromatosis type I present?
Cafe-au-lait spots (below)
Lisch nodules (pigmented iris hamartomas)
cutaneous neurofibromas (skin tumors of NF-1 are derived from neural crest cells)
optic gliomas
pheochromocytoma
Lisch nodules (as seen in NFM type I)
as seen in NFM type I
What causes NFM type I?
mutated NF1 tumor suppressor gene (neurofibromin, a negative regulator of RAS) on chromosome 17
How does VHL disease present?
Hemangioblastomas (high vascularity with hyperchromatic nuclei) in the retina, brain stem, cerebellum, and spine (below)
angiomatosis (e.g. cavernous hemangiomas in skin, mucosa, organs)
bilateral renal cell carcinomas
pheos
